Faculty Bibliography

Purpose: Bariatric surgery can achieve sustained weight loss compared to medical management. Among bariatric surgeries, laparoscopic adjustable gastric banding (LAGB) is less-invasive and potentially reversible. LAGB may decrease BMI through restriction of food intake, behavior changes, satiety and digestive hormone levels. The dramatic reduction of appetite observed with LAGB can be ameliorated if the band is underfilled. This effect has not been well evaluated in terms of patient behavior and hormonal changes. Our aim was to assess outcomes related to eating behavior, insulinotropic hormones, and weight change before and after temporary gastric band release. Methods: Adults >= 18 yeaars of age who previously underwent LAGB and achieved successful weight loss were enrolled. All patients underwent standardized evaluation including anthropometric measurements and completion of the Three-Factor Eating Questionnaire (TEFQ-R18) before and after a period of 14 days during which the band was completely loosened. At baseline and follow-up, blood was collected after an overnight fast and 1h after a standard high protein meal, and levels of insulinotropic hormones determined. Results: The mean age of the study cohort (9 women and 6 men) was 42 +/-14 years with mean pre-band adjustment BMI of 32.9 +/- 5.6 and mean waist circumference of 40 +/- 7 inches. All patients had >30% percent reduction in weight within 12-months of the LAGB and demonstrated a lower degree but continued weight loss in the 6-months before study enrollment. Compared to baseline values for the TEFQ-R18, within 2-weeks of loosening the band, cognitive restraint was reduced (11.2 +/- 3 vs. 10.4 +/- 4), while there was a significant increase in both disinhibition (6.4 +/- 3 vs. 9.4 +/- 3, p=0.004) and hunger scores (4.1 +/- 3 vs. 8.0 +/- 3, p=0.004). Compared to baseline, at follow-up insulin output in response to a meal showed a downward trend [Median (IQR) 1,110 (728-1,332) vs. 621 (375-1,325) pg/ml; p=0.21] while leptin was significantly elevated [10,400 (6,030-11,350) vs. 13,700 (10,500-43,900) pg/ml; p=0.001]. Consistent with these findings BMI significantly increased (32.9 +/- 5.6 vs. 34.5 +/- 5.6, p=0.001) along with waist size (40 +/- 7 vs 42 +/- 6, p=0.003). The amount of weight regained within two weeks, returned the cohort to the weight loss level noted at the 12-month post LAGB time point. Conclusion: LAGB adjustment continues to impact eating behavior, satiety hormones, and body weight beyond the initial 12-months following placement. Complete loosening of the LAGB can result in rapid changes in eating behavior, insulinotropic hormones, and significant changes in BMI. Careful adjustment of the band is necessary for continued maintenance of weight loss

Our aim was to examine the humoral immune response against Streptococcus gallolyticus subspecies gallolyticus antigens in individuals subjected to a routine colonoscopy in which colon adenomatous polyps were present or not. Serum samples from 133 individuals with adenomatous polyps and serum samples from 53 individuals with a normal colonoscopy were included. Western blot was performed in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and rabbit antisera against the whole cell bacteria was prepared as a control. By analyzing the immune profile of the rabbit-immunized sera by Western-blot, at least 22 proteins were identified as immunogenic in S. gallolyticus. When we evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa were most prominent. Based on this 2-protein band pattern, Western-blot profiles from human subjects were compared. The detection of a protein band of 22 kDa was associated with the presence of adenomatous polyps in colon [odds ratios (OR) 7.98, 95% confidence intervals (CI): 3.54-17.93], p < 0.001. When the presence of the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR increased to 22.37 (95% CI: 3.77-131.64), p < 0.001. The specificity was 84.9 for the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa protein alone or both 22 and 30 kDa bands. Serum from individuals with adenomatous polyps recognized two proteins from S. gallolyticus. This result confirmed the possible association of S. gallolyticus with adenomatous polyps in the colon.

Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-kappaB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus. Clin Cancer Res; 18(8); 2138-44. (c)2012 AACR.

Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.

ABSTRACT: BACKGROUND: The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. RESULTS: The average knowledge score was 37 +/- 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were 'patient refusal' and 'lack of insurance reimbursement.' CONCLUSIONS: There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer

Underrepresented minorities (URMs) make up a disproportionately small percentage of medical school applicants, matriculants, and physicians relative to the general US population. Preprofessional pipeline programs may help introduce URMs to careers in the medical field. MiniMeds was developed as a paracurricular enrichment program that targeted URM students. The curriculum was designed and administered by medical students, and 2 trials of this program were conducted. Data were collected pre and post program through a survey that assessed knowledge of medical concepts and knowledge of and interest in careers in medicine. Attendance at program sessions correlated with baseline knowledge about medical professions. Knowledge about medical concepts increased significantly from baseline to follow-up for boys, a group significantly represented by URMs in our cohort. Median scores for knowledge of medical careers increased significantly from baseline to followup for URMs as well as for boys and girls. Preprofessional pipeline programs such as MiniMeds are able to engage and develop medical knowledge in URM students at a critical developmental age. Further evaluation and implementation of programs that incorporate medical students to actively develop and lead pipeline programs are warranted.

Abstract Background and Purpose: Oxalobacter formigenes (OF) may play a protective role in preventing calcium oxalate stones. This is the first prospective study to evaluate the effect of antibiotics on OF colonization. Intestinal colonization by OF is associated with reduced urinary oxalate excretion. Exposure to antibiotics may be an important factor determining rates of colonization. Materials and Methods: The effect of antibiotics on OF colonization was compared in two groups: A group receiving antibiotics for gastric infection with Helicobacter pylori (HP) and a group without HP whose members were not receiving antibiotics. OF colonization in stool was detected by oxalate degradation at baseline and after 1 and 6 months. Results: The prevalence at baseline of intestinal colonization with OF was 43.1% among all patients screened. Among the 12 patients who were positive for OF who did not receive antibiotics, 11 (92%) had OF on stool tests at 1 month and 6 months. Of the 19 participants who were positive for OF and who received antibiotics for HP, only 7 (36.8%) continued to be colonized by OF on follow-up stool testing at 1 and 6 months (P=0.003 by Fisher exact test). Amoxicillin and clarithromycin caused 62.5% of subjects to become negative for OF at 1 month; 56.2% remained negative for OF at 6 months. Conclusions: Antibiotics for HP infection effectively reduced colonization with OF, an effect present at 1 and 6 months after treatment. The lasting elimination of OF could be associated with hyperoxaluria and be a factor in recurrent kidney stone disease

ABSTRACT: BACKGROUND: Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight. METHODS: Veterans referred for upper GI endoscopy were evaluated at baseline and >/=8 weeks after endoscopy, and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h after a standard high protein meal, and levels of eight hormones determined. RESULTS: Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate. Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed eradication. After a median of seven months following eradication, six hormones related to energy homeostasis showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI significantly increased (5 +/- 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not significantly changed in those who were H. pylori-negative or indeterminant at baseline. CONCLUSIONS: Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with consequent effects on body morphometry

Background: Physical activity may play an important role in the risk of colon cancer development. Studies that have observed a possible effect were either limited by the use of sigmoidoscopy alone, or did not include a diverse screening population. It remains unclear if the benefits of physical activity are protective against polyps located throughout the colon, and if these benefits are consistent across all ethnic groups. The aim of this study was to evaluate the relationship of exercise on the prevalence of polyps in a multiethnic CRC screening population. Methods: Consecutive average-risk adults referred for screening colonoscopy in a municipal hospital were prospectively enrolled. A detailed questionnaire was administered to collect data on medical, dietary, and exercise history. The number, size, and location of all polyps were documented during colonoscopy. Based on pathologic review, advanced neoplasms were defined as adenomas >= 10mm in diameter or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. Results: Among the 982 patients enrolled, 558 (56.8%) were Hispanic, 202 (20.6%) were Asian, 149 (15.2%) were African American, and 69 (7.0%) were Caucasian. BMI was abnormal (>=25) in 603 (61.4%) patients. 513 patients (52.2%) reported exercising at least one hour weekly. The median number of years of exercise was 5.0 years (IQR 1.5-10.0). The overall prevalence of colon polyps was 29.5%. Among patients who did not exercise at least one hour weekly the prevalence of polyps was 33.2%, while it was 25.3% in those who exercised one or more hours weekly (p=0.008). Among patients with a BMI>=25, at least one hour of weekly exercise was protective against any adenomas (OR 0.60, 95% CI 0.39-0.93) as well as any advanced adenomas (OR 0.37, 95% CI 0.16-0.88). Looking at racial/ethnic differences in the study group, the odds ratio for adenomas was lowest for Hispanics (OR 0.47, 95% CI 0.29-0.76) compared to their counterparts who exercised less. The odds ratio for advanced adenomas (>=1 cm) and carcinomas was lowest for African-Americans who exercised (0.16, 95% CI 0.03-0.77). In a logistic regression controlling for age, sex, race, and body mass index, one hour or more of weekly exercise remained protective against colonic polyps regardless of location, compared to those who exercised less (OR 0.69; 95% CI 0.52 - 0.91, p=0.009). Conclusion: In this multiethnic population, exercising at least one hour/week was associated with a lower prevalence of colonic polyps compared to those who exercised less or not at all. Polyps were less prevalent among overweight and obese individuals who exercised compared to those who did not exercise. Physical activity should be further evaluated as a preventative measure in colorectal cancer development

AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1gamma), Smad4 and transforming growth factor-beta (TGFbetaR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1gamma, Smad4 and TGFbetaRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1gamma was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFbetaRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1gamma overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1gamma overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1gamma occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome